Beyond the Numbers: Charting Chemical Reaction Space Paul M. Murray, Simon N. G. Tyler, and Jonathan D. Moseley Org. Process Res. Dev. ASAP
Fragment-based lead discovery grows up - News and Analysis Monya Baker NATURE REVIEWS, DRUG DISCOVERY, VOLUME 12, JANUARY 2013, page 5
Fragment-based hit identification: thinking in 3D Andrew D. Morley, Angelo Pugliese, Kristian Birchall, Justin Bower, Paul Brennan, Nathan Brown, Tim Chapman, Martin Drysdale, Ian H. Gilbert, Swen Hoelder, Allan Jordan, Steven V. Ley, Andy Merritt, David Miller, Martin E. Swarbrick, Paul G. Wyatt. Drug Discovery Today, asap. The identification of high-quality hits during the early phases of drug discovery is essential if projects are to have a realistic chance of progressing into clinical development and delivering marketed drugs. As the pharmaceutical industry goes through unprecedented change, there are increasing opportunities to collaborate via pre-competitive networks to marshal multifunctional resources and knowledge to drive impactful, innovative science. The 3D Fragment Consortium is developing fragment-screening libraries with enhanced 3D characteristics and evaluating their effect on the quality of fragment-based hit identification (FBHI) projects.
Plane of Best Fit: A Novel Method to Characterize the Three-Dimensionality of Molecules Nicholas C. Firth, Nathan Brown, and Julian Blagg, Journal of Chemical Information and Modelling ABSTRACT: We describe a computational method, plane of best fit (PBF), to quantify and characterize the 3D character of molecules. This method is rapid and amenable to analysis of large diverse data sets. We compare PBF with alternative literature methods used to assess 3D character and apply the method to diverse data sets of fragment-like, drug-like, and natural product compound libraries. We show that exemplar fragment libraries underexploit the potential of 3D character in fragment-like chemical space and that drug-like molecules in the libraries examined are predominantly 2D in character.
Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17 Lars Ruddigkeit, Ruud van Deursen, Lorenz C. Blum and Jean-Louis Reymond; J. Chem. Inf. Model., 2012, 52 (11), pp 2864–2875
Structural Biology and Drug Discovery of Difficult Targets: The Limits of Ligandability Surade, Sachin; Blundell, Tom L., Chemistry & Biology (2012), 19(1), 42-50
Using Fragment-Based Technologies to Target Protein-Protein Interactions Justin F. Bower and Andrew Pannifer; Current Pharmaceutical Design, Volume 18, Number 30, October 2012 , pp. 4685-4696(12)
Quantifying the chemical beauty of drugs Bickerton, G. Richard; Paolini, Gaia V.; Besnard, Jeremy; Muresan, Sorel; Hopkins, Andrew L., Nature Chemistry (2012), 4(2), 90-98
Design, Synthesis and Biological Evaluation of Trypanosoma brucei Trypanothione Synthetase Inhibitors Spinks, Daniel; Torrie, Leah S.; Thompson, Stephen; Harrison, Justin R.; Frearson, Julie A.; Read, Kevin D.; Fairlamb, Alan H.; Wyatt, Paul G.; Gilbert, Ian H., ChemMedChem (2012), 7(1), 95-106
Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors Brand, Stephen; Cleghorn, Laura A. T.; McElroy, Stuart P.; Robinson, David A.; Smith, Victoria C.; Hallyburton, Irene; Harrison, Justin R.; Norcross, Neil R.; Spinks, Daniel; Bayliss, Tracy; et al., Journal of Medicinal Chemistry (2012), 55(1), 140-152